A clinical herbalist may use mistletoe in a formula to treat a variety of conditions but it is not safe for home use. The safe prescribing of such a herb would be carefully considered in such cases. Herbalists often use mistletoe for conditions in the cardiovascular system.

Mistletoe is also manufactured as a pharmaceutical medication for cancer and HIV care (20). This is available in some European countries in the form of an injectable drug, the most common being Helixor®, Iscador®, abnobaVISCUM®. There are a small number of mistletoe therapy centres around the UK (22). Extensive research has been carried out on mistletoe and its bioactive compounds in relation to its effects on cancer. Much of this has been focused on the pharmacological actions of chemicals called viscotoxins, as well as a group of chemicals called lectins (1).

When mistletoe is taken orally, viscotoxins are less bioavailable, meaning that orally administered mistletoe delivers much smaller amounts of these to the body (19). Other medicinally active compounds such as flavonoids are more bioavailable as an oral medicine (19, 20).

Whilst mistletoe has a large body of evidence for a number of benefits in cancer treatment, it is important that people seeking to integrate herbal medicines into a care plan for serious conditions like cancer do so under the guidance of a qualified specialist.

Energetically, mistletoe is considered warming and astringent (11). Matthew Wood (14) discusses mistletoe in his book ‘The Earthwise Herbal’ in which he writes ‘mistletoe opens up circulation to areas that have been cut off from adequate blood supply by tension. It reduces cardiovascular tension and blood pressure, while bringing in new blood, blood sugar, and healing to areas long cut off, tensed up, weakened, or damaged’.

Mistletoe is also referenced in Wood’s writing as a nervine herb that promotes inward feeling, contemplation and reflection (14). It has a number of actions that directly affect the nervous system. It is also thought of as an antispasmodic and autonomic nervous system (ANS) balancer (15, 16). The ANS regulates automatic physiological processes such as heart rate, blood pressure, respiration and digestion as well as stress responses. 

Mistletoe has multiple, well-referenced applications for conditions which are directly associated with the ANS, such as high blood pressure (17) arrhythmia, insomnia, nervousness, anxiety, depression and nervous tension in the abdominal organs (15, 16, 17, 26).  Mistletoe is understood to reduce overactivity in the parasympathetic nervous system (PSNS) (27). Stableford (14) adds in his book, “The Handbook of Constitutional and Energetic Herbal Medicine” that mistletoe is specific for releasing emotional constraint.

According to Ms Grieve in ‘A Modern Herbal’, the traditional uses of mistletoe focused on conditions of the nervous system (9). Grieve discusses convulsions, hysteria, neuralgia, and complaints arising from ‘a weakened and disordered state of the nervous system’. A traditional formula of mistletoe, valerian, and vervain was given for ‘all kinds of nervous complaints’ (9).

In the early times of Western herbalism, mistletoe was used as a heart tonic. Traditional uses also include some cases of typhoid fever as a substitute for foxglove due to its ability to strengthen the heartbeat and increase heart rate (10). Greek physician Hippocrates and 17th-century herbalist Culpepper both referenced Mistletoe for use in treating disorders of the spleen (11).

The druids of ancient Britain were said to have applied mistletoe as a topical treatment for cancers. Both Pliny and Hippocrates also refer to its use for cancers and epilepsy. Pliny also comments further about the use of mistletoe by the Druids, who applied it as an antidote for all poisons. This is where it gained its folk name ‘all-heal’ (11).

Rudolf Steiner (an Austrian scientist and respected philosopher of his time) reintroduced the use of mistletoe extracts in the form of injections for the treatment of cancer in Western Europe in 1916 and the tradition continues in cancer clinics in Germany (11,12). Now his belief systems are highly controversial but his medical discoveries remain.

Nervous system

Mistletoe has an antispasmodic action (20, 26) and therefore may be indicated for conditions that present with spasmodic symptoms such as motor twitching, spasm, and nerve hyperactivity (20). A herbalist may incorporate mistletoe into a formula for patients where these types of symptoms are associated with nervous tension relating to stress and autonomic imbalance (imbalance of the autonomic nervous system). 

Mistletoe has a specific moderating action on the vagus nerve (20, 26). The vagus nerve is the main branch of the parasympathetic nervous system (PSNS) which is activated when we are relaxed for “rest and digest”. It is this action of the PSNS that allows mistletoe to moderate parasympathetic tone (20, 26). Some of the key roles of the parasympathetic system are to regulate the heart rate, moderate immune function and control of digestive processes.

Mistletoe has a number of known applications that correlate with PSNS activities, such as its ability to help strengthen a weak pulse and regulate the heart rate and blood pressure (20, 24).

Cardiovascular system

Perhaps one of mistletoe’s most prevalent uses by herbalists is for the treatment of hypertension (high blood pressure) (20). By contrast, its actions can also be useful for hypotension (low blood pressure). It has actions that allow it to moderate and balance, depending on what is required, a quality called ‘amphoteric’ (20).

Polyphenolics and triterpenoids are some of the major phytochemicals involved in mistletoe’s diuretic (increasing urination) and natriuretic (increasing sodium elimination in the urine) activity. These actions offer some explanation of its mechanism of action for hypertension (23).

It may elevate the blood pressure in hypotensive patients by strengthening the heart function i.e. the strength of the heart’s pumping action, as well as support for the integrity of the vasculature (20). Flavonoids found in mistletoe have demonstrated the ability to mitigate tachyarrhythmia and restore normal electrical conduction through the Purkinje fibres (fibres located in the heart that significantly contribute to electrical conduction and the transmission of impulses to the ventricular muscle). This action contributes to a reduction in ventricular excitability. They have also been shown to reduce noradrenalin-induced aortic contractions.

Traditionally, mistletoe has also been employed by herbalists to address symptoms associated with congestive heart failure, arrhythmia, and cardiac weakness, as well as their underlying causes, such as atherosclerosis and vascular inflammation. It exhibits the capacity to decelerate tachyarrhythmia or invigorate bradycardia. Indications for mistletoe include conditions such as cardiac enlargement, valvular incompetence, angina, shortness of breath, dyspnea, oedema, palpitation with exertion, and the inability to lie down. These symptoms collectively contribute to the broader spectrum of indications for mistletoe in the context of congestive heart disease (20).

For serious conditions like this, a herbalist may prescribe a formula with other supportive herbs for example cardiovascular tonics like bilberry or hawthorn. This would be in conjunction with lifestyle and dietary interventions to improve the systemic health of the patient.

Immune system

Mistletoe has a number of immunological actions, although much of the modern findings on this relate to mistletoe as an injectable medicine, which is not included in a herbalist’s practice. Compounds called lectins and viscotoxins in mistletoe are thought to be primarily responsible for its immunologic activity (1).

Mistletoe stimulates both innate and adaptive immune responses (1). Some of the immunological parameters observed to increase or improve with mistletoe include granulocytes (neutrophils, eosinophils, basophils), lymphocytes (T cells, B cells, NK cells), dendritic cells, cytokines and interleukins and IgG antibodies (20).

Mistletoe lectins are believed to have anticancer, immune-stimulating, and anti-inflammatory effects. Lectins also promote the release of cytokines, contributing to anti-inflammatory effects in the heart and other tissues, particularly the endothelium (the tissue that constitutes a single layer of cells lining various organs and cavities throughout the body) (20). 

Metabolism

Mistletoe has a number of references for use in metabolic conditions such as diabetes mellitus and metabolic syndrome, due to its ability to improve glycemic control and reduce vascular inflammation. Proteins in mistletoe have been shown to enhance insulin secretion from pancreatic cells (20). Mistletoe may also exhibit hypoglycemic and antioxidant effects, contributing to the protection of vasculature and enhancement of circulation (20).

This herb may be of particular use to herbalists where metabolic imbalances are accompanied by other conditions indicated for this herb.

Cancer care

The majority of research into the use of mistletoe in cancer care has been focused on clinically prescribed, injectable mistletoe extracts. Herbalists are not usually trained to administer injectable preparations and are more likely to use mistletoe tinctures or dried herb preparations in practice. When mistletoe is taken via oral administration it must pass through the gastrointestinal tract. The compounds most associated with mistletoe’s anti-cancer effects are lectins which are less bioavailable via oral administration. Therefore, information dealing with its effects in cancer treatment may not be applicable to the use of mistletoe by herbalists although mistletoe still possesses value in enhancing immune function via oral medications.

As an injectable medicine, mistletoe therapy has been shown to elicit a cytotoxic (eliminating cancerous cells) action in laboratory and animal studies by triggering cell death (2). Though a number of effects have been clearly demonstrated, further research including human clinical trials would help to establish a clearer picture of the potential of mistletoe as an anti-cancer medicine (20).

Mistletoe has however been shown to reduce the side effects of chemotherapy and radiation, as well as to improve quality of life (6). Mistletoe shows a clear effect in protecting the microcirculation against chemotherapy-induced damage (18, 20). 

There is limited evidence for its ability to reduce the growth and metastasis of cancerous tumours, though there are numerous studies that demonstrate specific anti-cancer mechanisms such as anti-angiogenesis (stopping the creation of blood vessels) that can help cancerous tumours grow. For this reason, mistletoe has been classified as a biological response modifier and anti-angiogenic (inhibits the tumour-induced formation of new blood vessels) (7,18).

Mistletoe is one of the best-researched herbal medicines in Europe (19). There is extensive research, including a number of clinical trials on mistletoe in cancer therapy. There are also in vivo and in vitro studies that focus on particular compounds (namely viscotoxins, which, in addition to lectins, belong to the important pharmaceutically active components of mistletoe).

Some of the mechanisms of action for cancer care have been identified in the current research. This includes immunomodulation of both innate and adaptive immune responses and direct cytotoxicity. Other actions demonstrated in laboratory studies include; increased lymphocytes (T cells, B cells, and NK cells), dendritic cells, cytokines including INF-gamma and IL6, and the presence of IgG antibodies to mistletoe lectins and viscotoxins (1).

The most conclusive studies effectively demonstrate that mistletoe extract used intravenously in cancer care can improve overall quality of life, reduce symptoms, and reduce side effects associated with treatment when given alongside standard cancer treatments (1). However, mistletoe is not a cancer cure, nor should it be thought of as an alternative to conventional treatments and must be taken with professional guidance. Further research is required in controlled studies to further elucidate its effects on survival and recurrence risk for cancer patients (1).

A number of these studies have been included below to demonstrate the mechanism of action for some of the medicinal actions of mistletoe discussed in this monograph, however, there is a lack of available human studies. Animal studies are not condoned by herbal reality, however, for the purpose of including research from which some understanding of therapeutic actions can be confirmed, some animal studies have been included herein.

Cancer

Mistletoe extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research

A systematic review was carried out to evaluate the available clinical studies and preclinical research on the therapeutic effectiveness and biological effects of mistletoe extracts on gynaecological and breast cancers. 19 randomised (RCT) and 16 non-randomised controlled studies (non RCT) were included as well as 11 single-arm cohort studies. They included 2420, 6399 and 1130 patients respectively. 12 of the randomised control trials reported a statistically significant benefit. 

A number of both RCTs and non-RCTs (3 and 6 respectively) demonstrated a clinically relevant change in tumour behaviour (remission or time to relapse) another 3 reported statistically significant improvements in tumour behaviour. Tumour remission was observed after high dosage and local application. 21 reported a statistically significant positive improvement in quality of life as well as tolerability of cancer treatments such as chemotherapy, radiotherapy or surgery (6). 

A clinical trial on the use of mistletoe therapy in patients with locally advanced or metastatic pancreatic cancer

A prospective, parallel, randomised phase 3 study was carried out to investigate the effects of mistletoe extract in patients with locally advanced or metastatic cancer of the pancreas. The study randomised 220 patients into two groups to either receive to subcutaneous injections of mistletoe extract (between 0.01 mg up to 10 mg three times per week) or a control.

The study demonstrated that the mistletoe group showed a significant improvement in overall survival ratings. The study concludes that mistletoe is a clinically relevant second-line therapy that has demonstrated effective disease-related symptom reduction in patients with locally advanced or metastatic pancreatic cancer (5).

Rectal cancer: A cohort study

A cohort study was carried out to establish the effect of mistletoe extract on tumour response in neoadjuvant chemoradiotherapy for rectal cancer. 52 Patients were administered mistletoe subcutaneously alongside chemoradiotherapy. 

There was a better tumour response in the mistletoe group in relation to the tumour regression grade and overall tumour–node–metastasis stage. This was also matched with a significantly improved tumour response and overall down staging. A higher level of apoptotic cells was observed in the mistletoe group samples. Overall patients treated with both chemoradiation and mistletoe had better outcomes than those who did not receive mistletoe (26).

A Case Report of a Patient with Bilateral Asynchronous Renal Cell Carcinoma and Lung Metastases: Treated Solely With High-dose Intravenous and Subcutaneous Mistletoe Extract

A 67-year-old man was diagnosed with grade 3/4 renal cell carcinoma in the right kidney. That patient’s history included a right nephrectomy and two lung metastasectomies in the preceding 6 years. A renal cell carcinoma lesion was later detected on the left kidney. The patient opted for treatment using only a high-dose intravenous and subsequent subcutaneous mistletoe extract after deciding to evade a further nephrectomy procedure. The patient showed no further progression during the following 2.5-year period, as well as good quality of life. This is an isolated case and the patient still showed an area of pertumeral halo surrounding an area of necrosis in the kidney tissue via ultrasound (21).

Intravenous mistletoe extract shows promise as cancer therapy in small study

An intravenous mistletoe extract known as Helixor M was studied in 21 patients with advanced and treatment-resistant cancers of various types. The study initially identified an optimum dose of 600 milligrams of mistletoe extract three times a week for a period of 15.3 weeks. 

The study showed that in three participants the tutor size decreased in size and remained stable for between two to five months. The results also showed overall improvements in quality of life identified through a patient questionnaire. Some side effects were also reported to include fatigue, nausea, and chills- these were all noted as manageable (2).

Immunosuppressed patients 

Tolerability of an extract of mistletoe among immunocompromised and healthy individuals

A dose-escalating phase 1 and phase 2 study was carried out to determine the biochemical effects of mistletoe extract on 32 human immunodeficiency virus (HIV) positive patients and 9 healthy participants. The mistletoe extract was standardised for its lectin and viscotoxin content.

Patients received the extract subcutaneously twice-weekly in gradually increasing doses of 0.01 mg to 10.0 mg for a period of between 2 to 17 weeks per dose increase. The study identified some minor side effects in the lower dose range which mainly affected the HIV patients. It was concluded that no serious adverse reactions were observed and that mistletoe induces immunomodulation in HIV-positive and healthy individuals and may inhibit the progression of HIV disease (8).

Greek mythological heroes were granted passage to the underworld with mistletoe. The druids believed that mistletoe would offer protection against evil and poisons. Mistletoe had a strong association with fertility and vitality through the Middle Ages, and is now understood to have oxytocic action (15, 25). Pagan societies thought it represented the divine male essence (4).

Mistletoe is native to the United Kingdom. It grows in the canopy of trees where there is optimum light. It is commonly found in apple, lime and poplar but has also been located on blackthorn, hawthorn, rowan and willow.

Although mistletoe is not endangered across Britain and Ireland, its population is declining. The annual Christmas harvest and trade of mistletoe has depended heavily on traditionally established English orchards. This source of mistletoe may now be threatened due to the continued decline of orchards across the British Isles (3, 4).

Habitat loss and over-harvesting from the wild are two of the biggest threats faced by medicinal plant species. There are an increasing number of well-known herbal medicines at risk of extinction. We must therefore ensure that we source our medicines with sustainability in mind. 

The herb supplement industry is growing at a rapid rate and until recent years a vast majority of medicinal plant produce in global trade was of unknown origin. There are some very real and urgent issues surrounding sustainability in the herb industry. These include environmental factors that affect the medicinal viability of herbs, the safety of the habitats that they are taken from, as well as the welfare of workers in the trade.

The botanical supply chain efforts for improved visibility (transparency and traceability) into verifiably sustainable production sites around the world are now certificated through the emergence of credible international voluntary sustainability standards (VSS). 

Read our article on  Herbal quality & safety: What to know before you buy and sustainable sourcing of herbs to learn more about what to look for and questions to ask suppliers about sustainability.

The proportion of bioactive compounds found in mistletoe varies throughout the year and also in relation to the host trees on which the mistletoe has grown. Some chemicals are present in higher concentrations in stems, others in leaves or berries, some more in female plants or in males or vice versa. The most potent are pharmacologically diverse extract of mistletoe is therefore made using a blend of plant material harvested in summer and winter and of that which grows (19).

In the pharmacological extracts of mistletoe often the host plant from which mistletoe was grown is usually indicated in the product name by a suffix letter. For example; IscadorM (from apple trees; Malus domestica); IscadorP (from pine trees; Pinus sylvestris); IscadorQu (from oak trees; Quercus robur); IscadorU (from elm trees; Ulmus minor) (1).

Herbal Medicines are often extremely safe to take, however it is important to buy herbal medicines from a reputed supplier. Sometimes herbs bought from unreputable sources are contaminated, adulterated or substituted with incorrect plant matter.

Some important markers for quality to look for would be to look for certified organic labelling, ensuring that the correct scientific/botanical name is used and that suppliers can provide information about the source of ingredients used in the product.

A supplier should be able to tell you where the herbs have come from. There is more space for contamination and adulteration when the supply chain is unknown.

Mistletoe seeds can be gathered during the season between November and February. To harvest your own seeds, you will need between 20-30 berries so that you can obtain a number of seeds to sow in different places to be sure you end up with both male and female plants (which makes it possible for the plant to reproduce).

• The seeds can be cultivated soon after harvesting. If you have stored your berries, you will need to rehydrate them by immersing overnight in a bowl of water.
• Once the berries have softened, they can be squeezed one at a time, so that a sticky jelly-like substance emerges along with the black seeds. Although the berries are harmless to touch- it is important to wash hands thoroughly after (unless gloves are worn) due to the toxic nature of the plant.
• Choose a host tree such as apple, lime, poplar or hawthorn. Shrubs of the Rosaceae family are also suitable. Spread the jelly-like viscin, complete with the seeds, onto a number of young branches (between 5 and 10cm in diameter). The best location for mistletoe is in the branches as high up in the tree and away from the centre of the tree (avoid the trunk).
• You may label the branches or mark them with a tag. This may also help to keep away hungry birds. No further care is required after sowing.
• Germination may occur between March or April. Some of the seeds will be eaten by birds or other wildlife, however there should be a number of successful seedlings will appear in early spring providing enough seeds have been planted.

Mistletoe is slow-growing and may take up to 3 years before the plant even develops its first leaves. From year 4, growth will accelerate for multiple branches will develop and finally in year 5, berries should start appearing.

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